BACKGROUND: Sex- and gender-associated differences determine the disease response to treatment. AIM: The study aimed to explore the hypothesis that progress in the management of STE-myocardial infarction (STEMI) overcomes the worse outcome in women. METHODS AND RESULTS: We performed an analysis of three randomized trials enrolling patients treated with primary PCI more than 10 years apart. PRAGUE-1,-2 validated the preference of transport for primary PCI over on-site fibrinolysis. PRAGUE-18 enrollment was ongoing at the time of the functional network of 24/7PCI centers, and the intervention was supported by intensive antiplatelets. The proportion of patients with an initial Killip ≥ 3 was substantially higher in the more recent study (0.6 vs. 6.7%, p = 0.004). Median time from symptom onset to the door of the PCI center shortened from 3.8 to 3.0 h, p < 0.001. The proportion of women having total ischemic time ≤3 h was higher in the PRAGUE-18 (OR [95% C.I.] 2.65 [2.03-3.47]). However, the percentage of patients with time-to-reperfusion >6 h was still significant (22.3 vs. 27.2% in PRAGUE-18). There was an increase in probability for an initial TIMI flow >0 in the later study (1.49 [1.0-2.23]), and also for an optimal procedural result (4.24 [2.12-8.49], p < 0.001). The risk of 30-day mortality decreased by 61% (0.39 [0.17-0.91], p = 0.029). CONCLUSION: The prognosis of women with MI treated with primary PCI improved substantially with 24/7 regional availability of mechanical reperfusion, performance-enhancing technical progress, and intensive adjuvant antithrombotic therapy. A major modifiable hindrance to achieving this benefit in a broad population of women is the timely diagnosis by health professional services.

Cardiocentre 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czechia

Department of Cardioangiology International Clinical Research Center St Anne's University Hospital Brno Brno Czechia

Department of Cardiology Charles University University Hospital in Pilsen Pilsen Czechia

Department of Cardiology Institute of Clinical and Experimental Medicine Prague Czechia

Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University General University Hospital Prague Czechia

Department of Internal and Cardiology Faculty of Medicine Masaryk University and University Hospital Brno Bohunice Brno Czechia

Institute of Biostatistics and Analyses Ltd Faculty of Medicine Masaryk University Brno Czechia

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Mehta L, Beckie T, DeVon H, Grines C, Krumholz H, Johnson M, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation. (2016) 133:916–47. 10.1161/CIR.0000000000000351 PubMed DOI

Pancholy S, Shantha G, Patel T, Cheskin L. Sex differences in short-term and long-term all-cause mortality among patients with ST-segment elevation myocardial infarction treated by primary percutaneous intervention: a meta-analysis. JAMA Intern Med. (2014) 174:1822–30. 10.1001/jamainternmed.2014.4762 PubMed DOI

Guo Y, Yin F, Fan C, Wang Z. Gender difference in clinical outcomes of the patients with coronary artery disease after percutaneous coronary intervention: a systematic review and meta-analysis. Medicine. (2018) 97:e11644. 10.1097/MD.0000000000011644 PubMed DOI PMC

Lansky A, Baron S, Grines C, Tremmel J, Al-Rame R, Angiolillo D, et al. SCAI expert consensus statement on sex-specific considerations in myocardial revascularization. J Soc Cardiovasc Angiogr Interv. (2022) 1:100016. PubMed PMC

Ventura-Clapier R, Dworatzek E, Seeland U, Kararigas G, Arnal J, Brunelleschi S, et al. Sex in basic research: concepts in the cardiovascular field. Cardiovasc Res. (2017) 113:711–24. 10.1093/cvr/cvx066 PubMed DOI

Stehli J, Martin C, Brennan A, Dinh D, Lefkovits J, Zaman S. Sex differences persist in time to presentation, revascularization, and mortality in myocardial infarction treated with percutaneous coronary intervention. J Am Heart Assoc. (2019) 8:e012161. 10.1161/JAHA.119.012161 PubMed DOI PMC

Sederholm Lawesson S, Isaksson R, Ericsson M, Ängerud K, Thylén I. SymTime Study Group. Gender disparities in first medical contact and delay in ST-elevation myocardial infarction: a prospective multicentre Swedish survey study. BMJ Open. (2018) 8:e020211. 10.1136/bmjopen-2017-020211 PubMed DOI PMC

Lüscher T, Miller V, Bairey Merz C, Crea F. Diversity is richness: why data reporting according to sex, age, and ethnicity matters. Eur Heart J. (2020) 41:3117–21. 10.1093/eurheartj/ehaa277 PubMed DOI PMC

Arora S, Stouffer G, Kucharska-Newton A, Qamar A, Vaduganathan M, Pandey A, et al. Twenty years trends and sex differences in young adults hospitalized with acute myocardial infarction. Circulation. (2019) 139:1047–56. 10.1161/CIRCULATIONAHA.118.037137 PubMed DOI PMC

Cushman M, Shay C, Howard V, Jiménez M, Lewey J, McSweeney J, et al. Ten-year differences in women’s awareness related to coronary heart disease: results of the 2019 American Heart Association National Survey: a special report from the American Heart Association. Circulation. (2021) 143:e239–48. 10.1161/CIR.0000000000000907 PubMed DOI PMC

Woodfield S, Lundergan C, Reiner J, Thompson M, Rohrbeck S, Deychak Y, et al. Gender and acute myocardial infarction: is there a different response to thrombolysis? J Am Col Cardiol. (1997) 29:35–42. 10.1016/s0735-1097(96)00449-4 PubMed DOI

Lansky A, Baron S, Grines C, Tremmel J, Al-Lamee R, Angiolillo D, et al. SCAI expert consensus statement on sex-specific considerations in myocardial revascularization. J Soc Cardiovasc Angiogr Interv. (2022) 1:100016. PubMed PMC

Widimsky P, Groch L, Zelizko M, Aschermann M, Bednar F, Suryapranata H. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J. (2000) 21:823–31. PubMed

Widimský P, Budesínský T, Vorác D, Groch L, Zelízko M, Aschermann M, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial–PRAGUE-2. Eur Heart J. (2003) 24:94–104. 10.1016/s0195-668x00468-2 PubMed DOI

Motovska Z, Hlinomaz O, Miklik R, Hromadka M, Varvarovsky I, Dusek J, et al. Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study. Circulation. (2016) 134:1603–12. 10.1161/CIRCULATIONAHA.116.024823 PubMed DOI

Stefanini G, Baber U, Windecker S, Morice M, Sartori S, Leon M, et al. Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials. Lancet. (2013) 382:1879–88. 10.1016/S0140-673661782-1 PubMed DOI

Motovska Z, Hlinomaz O, Kala P, Hromadka M, Knot J, Varvarovsky I, et al. 1-year outcomes of patients undergoing primary angioplasty for myocardial infarction treated with prasugrel versus ticagrelor. J Am Coll Cardiol. (2018) 71:371–81. 10.1016/j.jacc.2017.11.008 PubMed DOI

French J, White H. Clinical implications of the new definition of myocardial infarction. Heart. (2004) 90:99–106. 10.1136/heart.90.1.99 PubMed DOI PMC

Miller L, Marks C, Becker J, Hurn P, Chen W, Woodruff T, et al. Considering sex as a biological variable in preclinical research. FASEB J. (2017) 31:29–34. 10.1096/fj.201600781R PubMed DOI PMC

Haider A, Bengs S, Luu J, Osto E, Siller-Matula J, Muka T, et al. Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome. Eur Heart J. (2020) 41:1328–36. 10.1093/eurheartj/ehz898 PubMed DOI

Cenko E, Yoon J, Kedev S, Stankovic G, Vasiljevic Z, Krljanac G, et al. Sex differences in outcomes after STEMI: effect modification by treatment strategy and age. JAMA Intern Med. (2018) 178:632–9. 10.1001/jamainternmed.2018.0514 PubMed DOI PMC

Khera S, Kolte D, Gupta T, Subramanian K, Khanna N, Aronow W, et al. Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States. J Am Coll Cardiol. (2015) 66:1961–72. 10.1016/j.jacc.2015.08.865 PubMed DOI

Zandecki L, Sadowski M, Janion M, Gierlotka M, Gasior M, Polonski L. Trends in sex differences in clinical characteristics, treatment strategies, and mortality in patients with ST-elevation myocardial infarction in Poland from 2005 to 2011. Coron Artery Dis. (2017) 28:417–25. 10.1097/MCA.0000000000000504 PubMed DOI

Berg J, Björck L, Nielsen S, Lappas G, Rosengren A. Sex differences in survival after myocardial infarction in Sweden, 1987-2010. Heart. (2017) 103:1625–30. 10.1136/heartjnl-2016-310281 PubMed DOI PMC

Motovska Z, Widimsky P, Aschermann M. The impact of gender on outcomes of patients with ST elevation myocardial infarction transported for percutaneous coronary intervention: analysis of the PRAGUE-1 and 2 studies. Heart. (2008) 94:e5. 10.1136/hrt.2006.110866 PubMed DOI

Topol E, Kereiakes D. Regionalization of care for acute ischemic heart disease. Circulation. (2003) 107:1463–6. 10.1161/01.CIR.0000063680.45780.A0 PubMed DOI

Kalla K, Christ G, Karnik R, Malzer R, Norman G, Prachar H, et al. Implementation of guidelines improves the standard of care: the Viennese registry on reperfusion strategies in ST-elevation myocardial infarction (Vienna STEMI registry). Circulation. (2006) 113:2398–405. 10.1161/CIRCULATIONAHA.105.586198 PubMed DOI

Stehli J, Dinh D, Dagan M, Duffy S, Brennan A, Smith K, et al. Sex differences in prehospital delays in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. J Am Heart Assoc. (2021) 10:e019938. 10.1161/JAHA.120.019938 PubMed DOI PMC

Doktorova M, Motovska Z. Clinical review: bleeding – A notable complication of treatment in patients with acute coronary syndromes: incidence, predictors, classification, impact on prognosis, and management. Crit Care. (2013) 17:239. 10.1186/cc12764 PubMed DOI PMC

Mehran R, Chandrasekhar J, Urban P, Lang IM, Windhoevel U, Spaulding C, et al. Sex-based outcomes in patients with a high bleeding risk after percutaneous coronary intervention and 1-month dual antiplatelet therapy: a secondary analysis of the LEADERS FREE randomized clinical trial. JAMA Cardiol. (2020) 5:939–47. 10.1001/jamacardio.2020.0285 PubMed DOI PMC

Bhatt D. Percutaneous coronary intervention in 2018. JAMA. (2018) 319:2127–8. 10.1001/jama.2018.5281 PubMed DOI

Gaudino M, Di Franco A, Cao D, Giustino G, Bairey Merz C, Fremes S, et al. Sex-related outcomes of medical, percutaneous, and surgical interventions for coronary artery disease: JACC focus seminar 3/7. J Am Coll Cardiol. (2022) 79:1407–25. 10.1016/j.jacc.2021.07.066 PubMed DOI

Cenko E, van der Schaar M, Yoon J, Kedev S, Vavlukis M, Vasiljevic Z, et al. Sex-specific treatment effects after primary percutaneous intervention: a study on coronary blood flow and delay to hospital presentation. J Am Heart Assoc. (2019) 8:e011190. 10.1161/JAHA.118.011190 PubMed DOI PMC

Niccoli G, Montone R, Ibanez B, Thiele H, Crea F, Heusch G, et al. Optimized treatment of ST-elevation myocardial infarction. Circ Res. (2019) 125:245–58. 10.1161/CIRCRESAHA.119.315344 PubMed DOI

Meyer M, Bernheim A, Kurz D, O’Sullivan C, Tüller D, Zbinden R, et al. Gender differences in patient and system delay for primary percutaneous coronary intervention: current trends in a Swiss ST-segment elevation myocardial infarction population. Eur Heart J Acute Cardiovasc Care. (2019) 8:283–90. 10.1177/2048872618810410 PubMed DOI

Lau E, Braunwald E, Morrow D, Giugliano R, Antman E, Gibson C, et al. Sex, permanent drug discontinuation, and study retention in clinical trials: insights from the TIMI trials. Circulation. (2021) 143:685–95. 10.1161/CIRCULATIONAHA.120.052339 PubMed DOI PMC

Venetsanos D, Sederholm Lawesson S, Alfredsson J, Janzon M, Cequier A, Chettibi M, et al. Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised administration of ticagrelor in the catheterisation laboratory or in the ambulance for new ST elevation myocardial infarction to open the coronary artery (ATLANTIC) trial: a prespecified analysis. BMJ Open. (2017) 7:e015241. 10.1136/bmjopen-2016-015241 PubMed DOI PMC

Roswell R, Kunkes J, Chen A, Chiswell K, Iqbal S, Roe M, et al. Impact of sex and contact-to-device time on clinical outcomes in acute ST-segment elevation myocardial infarction-findings from the national cardiovascular data registry. J Am Heart Assoc. (2017) 6:e004521. 10.1161/JAHA.116.004521 PubMed DOI PMC

Pacheco C, Boivin-Proulx L, Bastiany A, Matteau A, Mansour S, Gobeil F, et al. Impact of STEMI diagnosis and catheterization laboratory activation systems on sex- and age-based differences in treatment delay. CJC Open. (2021) 3:723–32. 10.1016/j.cjco.2021.01.009 PubMed DOI PMC

Vogel B, Acevedo M, Appelman Y, Bairey Merz C, Chieffo A, Figtree G, et al. The lancet women and cardiovascular disease commission: reducing the global burden by 2030. Lancet. (2021) 397:2385–438. 10.1016/S0140-673600684-X PubMed DOI

Hausenloy D, Kharbanda R, Møller U, Ramlall M, Aarøe J, Butler R, et al. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet. (2019) 394:1415–24. 10.1016/S0140-673632039-2 PubMed DOI PMC

Ibanez B, Halvorsen S, Roffi M, Bueno H, Thiele H, Vranckx P, et al. Integrating the results of the CULPRIT-SHOCK trial in the 2017 ESC ST-elevation myocardial infarction guidelines: viewpoint of the task force. Eur Heart J. (2018) 39:4239–42. 10.1093/eurheartj/ehy294 PubMed DOI